Download THE GENUS MYCOBACTERIUM

THE GENUS
MYCOBACTERIUM
MYCOBACTERIUM
Aerobic
bacilli – non spore forming,
non motile
Cell
wall
Acid-fast
Very
–
bacilli
slow growing
rich in lipids
Mycobacteria:: Properties
Mycobacteria
Most
slow growing bacteria
Doubling time about one day
(20 hours)
Gram-positive, but don’t Gram stain
Mycolic acid cell wall
– acid fast staining
Positive
‘Acid-fast bacilli’
Generative (or doubling
doubling)) time
It is the time, covering the beginning of division of
the mother cell up to the formation of two new cells.
The average generative time is about 20 – 30
minutes in a majority of medically important
bacteria.
They are some exceptions among pathogenic
bacteria:
– Mycobacterium tuberculosis has the generative time
about 18 hours,
– Mycobacterium leprae has even much longer generative
time than other species (10 – 20 days).
The
mycobacteria, or acid-fast bacilli, are
responsible for tuberculosis and leprosy and a
number of saprophytic species occasionally
cause opportunist disease.
There
are about 50 species of mycobacteria,
which are divisible into two major groups, the
slow and rapid growers, atlhough the growth
rate of the latter is slow relative to that of most
other bacteria.
The
leprosy bacillus has never convincingly
been grown in vitro.
Mycobacterium
tuberculosis
Mycobacterium
tuberculosis causes the
infectious disease tuberculosis (TB).
Rod-like
obligate aerobe with filaments.
Mycobacterium
tuberculosis infects 1.7
million people world-wide
and causes 3 million deaths
each year, the most for any
single infectious disease.
After inhalation of the tubercle bacilli, the initial lesion
appears as an area of nonspecific pneumonitis. Delayed
hypersensitivity develops in 2 to 4 weeks resulting in
granulomatous inflammation and the characteristic
tubercles. The pulmonary focus and the granulomatous
lesion in the hilar lymph node are known as the primary
complex.
The next stage in the inflammatory process consists of
caseation necrosis. The caseous lesions heal by fibrosis and
calcification. The healed primary complex is referred to as
the Ghon focus. In a small minority of individuals, the
infection is not brought under control and the primary
lesions become larger, coalesce, and liquefy. When this
material is released, a cavity is formed in the lung.
Most
tuberculosis in adults is secondary to
reactivation of long-dormant foci remaining from
the primary infection. The foci are usually
located in the lung.
By
the time disease is recognised, liquefaction of
the caseous lesion has occurred and the resulting
cavity provides a favourable site for the rapid
proliferation of bacilli. These may then be
transmitted to other individuals via droplet nuclei
produced by aerosols of infected sputum.
Almost
every organ in the body may be the site
of extrapulmonary tuberculosis. The genitourinary, bones, joints, pleura, and peritoneum are
most commonly involved. Extrapulmonary
manifestations may also occur as a result of
reactivation of dormant lesions seeded during the
primary infection.
HIV
patients are particularly prone to
reactivation of pulmonary TB, the extent of
which depends on the amount of
immunosuppression. HIV-positive individuals
may also acquire new infection from others in
their environment.
Mycobacterium tuberculosis
Tuberculosis
is a chronic granulomatous
disease.
Mammalian
tuberculosis is caused by four
very closely related species:
– Mycobacterium tuberculosis (the human tubercle
bacillus)
– Mycobacterium bovis (the bovine tubercle
bacillus)
– Mycobacterium microti (the vole tubercle
bacillus)
– Mycobacterium africanum
M. tuberculosis causes tuberculosis but other species of
mycobacteria also cause infection in the lungs. These are
called the "atypical mycobacteria", "non-tuberculous
mycobacteria" or "mycobacteria other than tuberculosis MOTT".
Tuberculosis is a killer and ranks as one of the most serious
infectious diseases of the developing world. This has
become particularly obvious in patients with AIDS.
Tuberculosis is primarly a disease of the lungs but may
spread to other sites or proceed to a generalized infection
("miliary tuberculosis").
Infection is acquired by inhalation of M. tuberculosis in
aerosols and dust. Airborne transmission of tuberculosis is
efficient because infected people cough up enormous
number of mycobacteria.
Most human tuberculosis is caused by M.
tuberculosis but some cases are due to M. bovis,
which is the principal cause of tuberculosis in cattle
and many other mammals.
The name M. africanum is given to tubercle bacilli
with rather variable properties and which appear to
be intermediate in form between the human and
bovine types. It causes human tuberculosis and is
mainly found in Equatorial Africa.
M. microti is seldom, if ever, encountered
nowadays.
Anti--tuberculous agents
Anti
The treatment of infection caused by Mycobacterium
tuberculosis and other mycobacteria presents an
enormous challenge to medicine and pharmaceutical
industry.
They grow and multiply extremely slowly and effective
inhibition takes months.
A number of anti-tuberculous agents are now available.
Most are restricted to this use to present resistance
emerging in other species and potentially being
transferred to mycobacteria or because the toxicity of
the drugs makes them unattractive for general use.
Treatment of TB
• Initiate four drugs
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol or Streptomycin
- Adjust regimen when drug susceptibility results
known
- Total treatment usually 8 weeks of 4 drugs + 16
weeks of 2 drugs = 24 weeks total
Treatment regimens may vary between countries
in general
Mycobacterium leprae
Acid fast bacilli
Strict human pathogens
Cannot be cultivated in-vitro
Transmission - ? Air borne
Low infectivity - prolonged contact required
Spectrum of clinical presentations
– dependent on host –parasite interactions
Tuberculoid
Borderline
tuberculoid
Borderline
lepromatous
Lepromatous
Mycobacterium leprae
- pathogenesis
M. leprae causes granulomatous lesions resembling those of
tuberculosis, with epitheloid and giant cells but without caseation.
The organisms are predominantly intracellular and can proliferate
within macrophages, like tubercle bacilli.
Leprosy is distinguished by its chronic slow process.
The organism has a predilection for skin and nerves. In the
cutaneous form of the disease, large firm nodules are distributed
widely and on the face they create a characteristic leonine
appearance. In the neural form, segments of peripheral nerves are
involved, more or less as random, leading to localised patches of
anaesthesia. The loss of sensation in the fingers increases the
frequency of minor trauma, leading to secondary infection and
mutilating injuries.
Treatment of leprosy
Infection caused by M. leprae is characterized by
persistence of the microorganism in the tissues for
years, necessitates very prolonged treatment to
prevent relapse.
For many years dapsone, a sulphone derivative has
been used. This drug has the advantage that it is
given orally and it is cheap and effective.
However, widespread use as monotherapy has
resulted in the emergence of resistance and
multidrug regimens are therefore preferable.
Rifampicin can be combined with dapsone.
Alternatively clofazime is active against dapsoneresistant M. leprae, but it is expensive.
In
addition to the tubercle and leprosy
bacilli there are many species of
mycobacteria that normally exist as
saprophytes of soil and water.
Some
of these, termed environmental
or „atypical“ mycobacteria,
occasionally cause opportunist disease
in animal and man.
Diseases due to atypical mycobacteria:
mycobacteria:
skin
lesions following traumatic inoculation of
bacteria,
localized
lymphadenitis,
tuberculosis-like
disseminated
pulmonary lesions,
disease.